Study based at UW raises hopes for Zika vaccine, immunity

A vacuum tube holds a blood-fed strain of Aedes aegypti mosquito in place under a microscope in a research lab insectary in the Hanson Biomedical Sciences Building at the University of Wisconsin-Madison. Matthew Aliota, assistant scientist in the Department of Pathobiological Sciences in the School of Veterinary Medicine, is studying the insect as part of his research about mosquito-borne pathogens such as the Zika virus, dengue fever and yellow fever infections. Credit: Jeff Miller/UW-Madison

New experiments have shown that one infection with Zika virus can provide immunity against subsequent exposure to the virus, a piece of good news published Tuesday as officials continue to wrestle with the mosquito-borne threat.

The results, published in the journal Nature Communications,are the result of a collaboration between scientists at the University of Wisconsin-Madison and Duke University that was led by UW-Madison professor David O'Connor. The study used monkeys as a model for how Zika might affect humans, and also explored the role of pregnancy in infection.

The findings bode well for the development of a Zika vaccine and provide hope for people who have already been infected.

As of June 22, 61 countries have reported cases of Zika virus. Infection with Zika during pregnancy has been linked to development disorders of the nervous system that can result in a small head, or microcephaly, in newborns. Children born with microcephaly can experience problems with movement, vision, hearing, swallowing and intellectual development.

"You may have to follow children for five years or longer to tell whether there is cognitive impairment in their development," Matthew Aliota, a first author on the study and assistant scientist in pathobiological sciences at UW-Madison, said in a news release Tuesday. "But it's something you can answer with macaques relatively quickly, and that speed is very important in the context of an epidemic."

Animal models are necessary to conduct experiments into how Zika causes birth defects. In early Zika studies, mice with weakened immune systems were used. However, they exhibited different reactions to the virus from humans — particularly in how the virus altered blood flow — that compromised their usefulness.

Macaques, on the other hand, share high genetic similarity with humans and undergo a similar gestation as humans.

"With this model, we can try to address how infection during pregnancy leads to fetal abnormalities," O'Connor said. "That is the most important question. What we don't know is the extent to which babies are going to be affected."

Eight monkeys, two of which were pregnant, were injected with the same type of Zika virus circulating in South America, at equivalent doses to the estimated viral levels in mosquito saliva during a bite. Virus was detected in the plasma, urine and saliva of each monkey for about 10 days after injection in the nonpregnant monkeys, which proved that Zika can infect and replicate in the macaques. The monkeys also mounted a detectable immune response against the virus.

In the two monkeys that were infected in the first trimester of pregnancy, the virus was detectable up to 70 days after infection. This persistence through pregnancy could explain why the virus causes birth defects, and might even indicate that the fetus remains infected long after the mother clears the virus from her system.

When these monkeys were injected with another dose of virus 10 weeks later, no virus was detected in any blood or bodily fluids. The immune response mounted against the initial infection was sufficient to prevent reinfection.

"This is a key finding because it means that a vaccine could be quite effective against the virus," said Dawn Dudley, a co-author on the study.

"In Africa, where the virus has been circulating for an extended period of time, they haven't seen these adverse outcomes in pregnancy," Aliota said. "That seems to be because people are primarily exposed early in life, develop immunity, and then are protected later in life when they have children."

All of which, according to O'Connor, is good news for all the people who have contracted Zika already.

"A lot of people will be infected with Zika this summer and next. The indication is that they will develop immunity. This is unlikely to be a chronic infectious disease threat, but we still need research to prevent as many abnormalities as possible in the next five years."

O'Connor is part of a group of scientists who are making the results of their Zika studies available to the public in real time to support collaborative research.

"An additional benefit was that by making the data available online, we were able to design experiments collaboratively with other groups to use as few animals as possible to answer these important research questions."